A total of three people are reported killed in the drive-by shooting near the West Bank settlement of Alon Shvut, in the Etzion Bloc.
One of those killed is an 18-year-old Israeli, another is reported to be a US national, and the third is a Palestinian man.
A 50-year-old man is in critical condition at the Hadassah Ein Karem hospital in Jerusalem. At least five more people are wounded in the attack.
Two suspects are subdued by security forces and detained by police.